Bernelin-Cottet Cindy, Deloizy Charlotte, Stanek Ondrej, Barc Céline, Bouguyon Edwige, Urien Céline, Boulesteix Olivier, Pezant Jérémy, Richard Charles-Adrien, Moudjou Mohammed, Da Costa Bruno, Jouneau Luc, Chevalier Christophe, Leclerc Claude, Sebo Peter, Bertho Nicolas, Schwartz-Cornil Isabelle
VIM-INRA-Université Paris-Saclay , Jouy-en-Josas , France.
Institute of Microbiology of the Czech Academy of Sciences, v.v.i , Prague , Czech Republic.
Front Immunol. 2016 Dec 26;7:641. doi: 10.3389/fimmu.2016.00641. eCollection 2016.
The development of influenza A virus (IAV) vaccines, which elicits cross-strain immunity against seasonal and pandemic viruses is a major public health goal. As pigs are susceptible to human, avian, and swine-adapted IAV, they would be key targets of so called universal IAV vaccines, for reducing both the zoonotic risk and the economic burden in the swine industry. They also are relevant preclinical models. However, vaccination with conserved IAV antigens (AGs) in pigs was reported to elicit disease exacerbation. In this study, we assessed whether delivery strategies, i.e., dendritic cell (DC) targeting by the intradermal (ID) or intramuscular (IM) routes, impact on the outcome of the vaccination with three conserved IAV AGs (M2e, NP, and HA2) in pigs. The AGs were addressed to CD11c by non-covalent binding to biotinylated anti-CD11c monoclonal antibody. The CD11c-targeted AGs given by the ID route exacerbated disease. Conversely, CD11c-targeted NP injected by the IM route promoted T cell response compared to non-targeted NP. Furthermore, the conserved IAV AGs injected by the IM route, independently of DC targeting, induced both a reduction of viral shedding and a broader IgG response as compared to the ID route. Our findings highlight in a relevant animal species that the route of vaccine delivery impacts on the protection induced by conserved IAV AGs and on vaccine adverse effects. Finally, our results indicate that HA2 stands as the most promising conserved IAV AG for universal vaccine development.
开发能引发针对季节性和大流行病毒的交叉毒株免疫力的甲型流感病毒（IAV）疫苗是一项主要的公共卫生目标。由于猪易感染人源、禽源和猪源适应性IAV，它们将成为所谓通用IAV疫苗的关键靶点，以降低人畜共患病风险和养猪业的经济负担。它们也是相关的临床前模型。然而，据报道，用保守的IAV抗原（AGs）给猪接种疫苗会导致疾病加重。在本研究中，我们评估了递送策略，即通过皮内（ID）或肌肉内（IM）途径靶向树突状细胞（DC），是否会影响用三种保守的IAV AGs（M2e、NP和HA2）给猪接种疫苗的结果。通过与生物素化抗CD11c单克隆抗体非共价结合，将AGs靶向CD11c。通过ID途径给予的靶向CD11c的AGs会加重疾病。相反，与非靶向NP相比，通过IM途径注射的靶向CD11c的NP促进了T细胞反应。此外，与ID途径相比，通过IM途径注射的保守IAV AGs，无论是否靶向DC，都能减少病毒脱落并诱导更广泛的IgG反应。我们的研究结果在一个相关动物物种中突出表明，疫苗递送途径会影响保守IAV AGs诱导的保护作用以及疫苗不良反应。最后，我们的结果表明，HA2是通用疫苗开发中最有前景的保守IAV AG。
